Many environmental mutagens and carcinogens are known to interact with cellular DNA and RNA in vivo. In these studies, synthetic oligonucleotides and polynucleotides will be used as models for nucleic acids to determine the significance of such interactions. This approach uses simple, well-defined systems to yield detailed information on the chemistry of base substitution and on the consequences of these structural alterations. Biological effects will be assayed in biosynthetic systems which utilize the reacted polynucleotides as templates for replicating and transcribing enzymes. In this way, evidence is obtained as to the information, or misinformation, contained by the altered base. Investigations will proceed along four lines: (a) the study of certain known substitutions, e.g., on the 0-6 position of guanine, which are believed to have special biological significance; (b) an investigation of the repair of these lesions; (c) the structural elucidation and biological study of new derivatives; and (d) the development of a screening method for detecting the biological effects of interactions with suspected carcinogens.